Reasoning Report: Engineering Case Conferences to Maximize Clinical Reasoning Education for All Learners.

Case conferences, specifically those in which an unknown case is presented and discussed, are widely utilized in the delivery of medical education. However, the format of case conferences is not always optimized to engage and challenge audience members' clinical reasoning (CR). Based on the current conception of CR and our experience, we provide recommendations on how to better engineer case conferences to maximize CR education for learners at all levels through case selection, conference format, and intentional case construction.

Beyond thinking fast and slow: Implications of a transtheoretical model of clinical reasoning and error on teaching, assessment, and research.

From dual process to a family of theories known collectively as situativity, both micro and macro theories of cognition inform our current understanding of clinical reasoning (CR) and error. CR is a complex process that occurs in a complex environment, and a nuanced, expansive, integrated model of these theories is necessary to fully understand how CR is performed in the present day and in the future. In this perspective, we present these individual theories along with figures and descriptive cases for purposes of comparison before exploring the implications of a transtheoretical model of these theories for teaching, assessment, and research in CR and error.

'We're like Spider-Man; with great power comes great responsibility': Coaches' experiences supporting struggling medical students.

BACKGROUND: Medical students can experience a range of academic and non-academic struggles. Coaching is a valuable strategy to support learners, but coaches describe working with struggling learners as taxing. Transformative learning theory (TLT) provides insights into how educators grow from challenging experiences to build resilience. This study explores how coaches evolve as educators through supporting struggling students. METHODS: This qualitative study grounded in an interpretivist paradigm used interviews of longitudinal medical student coaches at two academic institutions. Interviews, using TLT as a sensitizing concept, explored coaches' experience coaching struggling learners. We performed thematic analysis. RESULTS: We interviewed 15 coaches. Coaches described supporting students through multi-faceted struggles which often surprised the coach. Three themes characterized coaches' experiences: personal responsibility, emotional response, and personal learning. Coaches shouldered high personal responsibility for learners' success. For some, this burden felt emotional, raised parental instincts and questions about maintaining boundaries with learners. Coaches evolved their coaching approach, challenged biases, and built skills. Coaches learned to better appreciate the learner point of view and employ resources to support students. DISCUSSION: Through navigating learner struggles, educators can gain self-efficacy, learn to understand learners' perspectives, and evolve their coaching approach to lessen their personal emotional burden through time.

Influence of a Large Language Model on Diagnostic Reasoning: A Randomized Clinical Vignette Study.

Importance: Diagnostic errors are common and cause significant morbidity. Large language models (LLMs) have shown promise in their performance on both multiple-choice and open-ended medical reasoning examinations, but it remains unknown whether the use of such tools improves diagnostic reasoning. Objective: To assess the impact of the GPT-4 LLM on physicians' diagnostic reasoning compared to conventional resources. Design: Multi-center, randomized clinical vignette study. Setting: The study was conducted using remote video conferencing with physicians across the country and in-person participation across multiple academic medical institutions. Participants: Resident and attending physicians with training in family medicine, internal medicine, or emergency medicine. Interventions: Participants were randomized to access GPT-4 in addition to conventional diagnostic resources or to just conventional resources. They were allocated 60 minutes to review up to six clinical vignettes adapted from established diagnostic reasoning exams. Main Outcomes and Measures: The primary outcome was diagnostic performance based on differential diagnosis accuracy, appropriateness of supporting and opposing factors, and next diagnostic evaluation steps. Secondary outcomes included time spent per case and final diagnosis. Results: 50 physicians (26 attendings, 24 residents) participated, with an average of 5.2 cases completed per participant. The median diagnostic reasoning score per case was 76.3 percent (IQR 65.8 to 86.8) for the GPT-4 group and 73.7 percent (IQR 63.2 to 84.2) for the conventional resources group, with an adjusted difference of 1.6 percentage points (95% CI -4.4 to 7.6; p=0.60). The median time spent on cases for the GPT-4 group was 519 seconds (IQR 371 to 668 seconds), compared to 565 seconds (IQR 456 to 788 seconds) for the conventional resources group, with a time difference of -82 seconds (95% CI -195 to 31; p=0.20). GPT-4 alone scored 15.5 percentage points (95% CI 1.5 to 29, p=0.03) higher than the conventional resources group. Conclusions and Relevance: In a clinical vignette-based study, the availability of GPT-4 to physicians as a diagnostic aid did not significantly improve clinical reasoning compared to conventional resources, although it may improve components of clinical reasoning such as efficiency. GPT-4 alone demonstrated higher performance than both physician groups, suggesting opportunities for further improvement in physician-AI collaboration in clinical practice.

Lessons in clinical reasoning - pitfalls, myths, and pearls: a case of tarsal tunnel syndrome caused by an intraneural ganglion cyst.

OBJECTIVES: Intraneural ganglionic cysts are non-neoplastic cysts that can cause signs and symptoms of peripheral neuropathy. However, the scarcity of such cases can lead to cognitive biases. Early surgical exploration of space occupying lesions plays an important role in identification and improving the outcomes for intraneural ganglionic cysts. CASE PRESENTATION: This patient presented with loss of sensation on the right sole with tingling numbness for six months. A diagnosis of tarsal tunnel syndrome was made. Nerve conduction study revealed that the mixed nerve action potential (NAP) was absent in the right medial and lateral plantar nerves. The magnetic resonance imaging (MRI) found a cystic lesion measuring 1.4×1.8×3.8 cm as the presumed cause of the neuropathy. Surgical exploration revealed a ganglionic cyst traversing towards the flexor retinaculum with baby cysts. The latter finding came as a surprise to the treating surgeon and was confirmed to be an intraneural ganglionic cyst based on the histopathology report. CONCLUSIONS: Through integrated commentary by a case discussant and reflection by an orthopedician, this case highlights the significance of the availability heuristic, confirmation bias, and anchoring bias in a case of rare disease. Despite diagnostic delays, a medically knowledgeable patient's involvement in their own care lead to a more positive outcome. A fish-bone diagram is provided to visually demonstrate the major factors that contributed to the diagnostic delay. Finally, this case provides clinical teaching points in addition to a pitfall, myth, and pearl related to availability heuristic and the sunk cost fallacy.

Development and Validation of a Formative Assessment Tool for Nephrology Fellows' Clinical Reasoning.

BACKGROUND: Diagnostic errors are commonly driven by failures in clinical reasoning. Deficits in clinical reasoning are common among graduate medical learners, including nephrology fellows. We created and validated an instrument to assess clinical reasoning in a national cohort of nephrology fellows and established performance thresholds for remedial coaching. METHODS: Experts in nephrology education and clinical reasoning remediation designed an instrument to measure clinical reasoning through a written patient encounter note from a web-based, simulated AKI consult. The instrument measured clinical reasoning in three domains: problem representation, differential diagnosis with justification, and diagnostic plan with justification. Inter-rater reliability was established in a pilot cohort ( n =7 raters) of first-year nephrology fellows using a two-way random effects agreement intraclass correlation coefficient model. The instrument was then administered to a larger cohort of first-year fellows to establish performance standards for coaching using the Hofstee method ( n =6 raters). RESULTS: In the pilot cohort, there were 15 fellows from four training program, and in the study cohort, there were 61 fellows from 20 training programs. The intraclass correlation coefficients for problem representation, differential diagnosis, and diagnostic plan were 0.90, 0.70, and 0.50, respectively. Passing thresholds (% total points) in problem representation, differential diagnosis, and diagnostic plan were 59%, 57%, and 62%, respectively. Fifty-nine percent ( n =36) met the threshold for remedial coaching in at least one domain. CONCLUSIONS: We provide validity evidence for a simulated AKI consult for formative assessment of clinical reasoning in nephrology fellows. Most fellows met criteria for coaching in at least one of three reasoning domains, demonstrating a need for learner assessment and instruction in clinical reasoning.

Lessons in clinical reasoning - pitfalls, myths, and pearls: a case of crushing, substernal chest pain.

OBJECTIVES: Diagnostic error is not uncommon and diagnostic accuracy can be improved with the use of problem representation, pre-test probability, and Bayesian analysis for improved clinical reasoning. CASE PRESENTATION: A 48-year-old female presented as a transfer from another Emergency Department (ED) to our ED with crushing, substernal pain associated with dyspnea, diaphoresis, nausea, and a tingling sensation down both arms with radiation to the back and neck. Troponins were elevated along with an abnormal electrocardiogram. A negative myocardial perfusion scan led to the patient's discharge. The patient presented to the ED 10 days later with an anterior ST-elevation myocardial infarction. CONCLUSIONS: An overemphasis on a single testing modality led to diagnostic error and a severe event. The use of pre-test probabilities guided by history-taking can lead to improved interpretation of test results, ultimately improving diagnostic accuracy and preventing serious medical errors.

Framework and Schema are False Synonyms: Defining Terms to Improve Learning.

Clinical reasoning is an essential expertise of health care professionals that includes the complex cognitive processes that lead to diagnosis and management decisions. In order to optimally teach, learn, and assess clinical reasoning, it is imperative for teachers and learners to have a shared understanding of the language. Currently, educators use the terms schema and framework interchangeably but they are distinct concepts. In this paper, we offer definitions for schema and framework and use the high-stakes field of aviation to demonstrate the interplay of these concepts. We offer examples of framework and schema in the medical education field and discuss how a clear understanding of these concepts allows for greater intentionality when teaching and assessing clinical reasoning.

A novel virtual course to teach medical students high-value decision-making.

BACKGROUND: Although a clinician's ability to employ high-value decision-making is influenced by training, many undergraduate medical education programmes lack a formal curriculum in high-value, cost-conscious care. We present a curriculum developed through a cross-institutional collaboration that was used to teach students at two institutions about this topic and can serve as a framework for other institutions to develop similar curricula. APPROACH: The faculty from the University of Virginia and the Johns Hopkins University School of Medicine created a 2-week-long online course to teach medical students the fundamentals of high-value care. The course consisted of learning modules, clinical cases, textbook studies, journal clubs and a competitive 'Shark Tank' final project where students proposed a realistic intervention to promote high-value clinical care. EVALUATION: Over two-thirds of students rated the course's quality as excellent or very good. Most found the online modules (92%), assigned textbook readings (89%) and 'Shark Tank' competition (83%) useful. To evaluate the student's ability to apply the concepts learned during the course in clinical contexts, we developed a scoring rubric based on the New World Kirkpatrick Model to evaluate students' proposals. Groups chosen as finalists (as determined by faculty judges) were more likely to be fourth-year students (56%), achieved higher overall scores (p = 0.03), better incorporated cost impact at several levels (patient, hospital and national) (p = 0.001) and discussed both positive and negative impacts on patient safety (p = 0.04). IMPLICATIONS: This course provides a framework for medical schools to use in their teaching of high-value care. Cross-institutional collaboration and online content overcame local barriers such as contextual factors and lack of faculty expertise, allowed for greater flexibility, and enabled focused curricular time to be spent on a capstone project competition. Prior clinical experience amongst medical students may be an enabling factor in promoting application of learning related to high-value care.

Dialysis Disequilibrium Syndrome and Intracranial Pressure Fluctuations in Neurosurgical Patients Undergoing Renal Replacement Therapy: Systematic Review and Pooled Analysis.

BACKGROUND: Dialysis disequilibrium syndrome is a rare, well-known, potentially life-threatening complication of renal replacement therapy (RRT), often involving cerebral edema and increased intracranial pressure (ICP). However, the impact of RRT on ICP and rate of dialysis disequilibrium syndrome in neurosurgical patients have not been systematically assessed. METHODS: In February 2022, a systematic review following PRISMA guidelines was conducted using various combinations of 9 keywords in the MEDLINE database. Eleven papers were selected. Individual patient data were extracted, pooled, and analyzed. RESULTS: Fifty-eight patients, 44 men and 14 women with a mean age of 48 years (6-78 years), were analyzed. Neurosurgical conditions included the following: spontaneous intracranial hemorrhage (n = 27), traumatic brain injury (n = 16), ischemic stroke/anoxic brain injury (n = 6), intracranial tumor (n = 6), and others (n = 3). Neurosurgical interventions included the following: craniotomy/craniectomy (n = 23), external ventricular drain or ICP monitor placement (n = 16), and burr hole or twist drill craniostomy (n = 4). Intermittent dialysis was used in 33 patients, continuous RRT in 20, and a combination thereof in 4. During RRT, ICP increased in 35 patients (60.3%), remained unchanged in 20, and decreased in 3. Thirty-four patients (65.4%) died. Intermittent dialysis was associated with increased ICP (73% vs. 37.5%, P = 0.01) and mortality (75% vs. 39.1%, P = 0.01). CONCLUSIONS: In neurosurgical patients, ICP increases during RRT are common, affecting up to 60%, and potentially life-threatening, with mortality rates as high as 65%. The use of a continuous rather than intermittent RRT technique may reduce the risk of this complication. Prospective studies are warranted.

The future of teaching management reasoning: important questions and potential solutions.

Management reasoning is distinct from but inextricably linked to diagnostic reasoning in the iterative process that is clinical reasoning. Complex and situated, management reasoning skills are distinct from diagnostic reasoning skills and must be developed in order to promote cogent clinical decisions. While there is growing interest in teaching management reasoning, key educational questions remain regarding when it should be taught, how it can best be taught in the clinical setting, and how it can be taught in a way that helps mitigate implicit bias. Here, we describe several useful tools to structure teaching of management reasoning across learner levels and educational settings. The management script provides a scaffold for organizing knowledge around management and can serve as a springboard for discussion of uncertainty, thresholds, high-value care, and shared decision-making. The management pause reserves space for management discussions and exploration of a learner's reasoning. Finally, the equity reflection invites learners to examine management decisions from a health equity perspective, promoting the practice of metacognition around implicit bias. These tools are easily deployable, and - when used regularly - foster a learning environment primed for the successful teaching of management reasoning.

Understanding the role of placental pathophysiology in the development of bronchopulmonary dysplasia.

The associations between bronchopulmonary dysplasia (BPD) and the gestational pathologies of chorioamnionitis (CA) and hypertensive disorders of pregnancy (HDP) have become increasingly well recognized. However, the mechanisms through which these antenatal conditions cause increased risk of BPD remain less well characterized. The objective of this review is to discuss the role of the placenta in BPD predisposition as a primary driver of intrauterine alterations adversely impacting fetal lung development. We hypothesize that due to similarities in structure and function, placental disorders during pregnancy can uniquely impact the developing fetal lung, creating a unique placental-pulmonary connection. In the current review, we explore this hypothesis through analysis of clinical literature and preclinical model systems evaluating BPD predisposition, discussion of BPD phenotypes, and an overview on strategies to incorporate placental investigation into research on fetal lung development. We also discuss important concepts learned from research on antenatal steroids as a modulator fetal lung development. Finally, we propose that the appropriate selection of animal models and establishment of in vitro lung developmental model systems incorporating primary human placental components are key in continuing to understand and address antenatal predisposition to BPD.

L-DOPA coating improved phosphate glass fibre strength and fibre/matrix interface.

The levodopa (L-DOPA) has been reported as a promising adhesive for various materials. In this study, we utilized L-DOPA as an interfacial agent for phosphate glass fibre/polycaprolactone (PGF/PCL) composites, with the aim to enhance the interfacial properties between the fibres and polymer matrix. The PGFs were dip-coated in varying concentrations of L-DOPA solution ranging between 5 and 40 g L-1. The fibre strength and interfacial shear strength (IFSS) of the composites were measured via a single fibre tensile test and single fibre fragmentation test, respectively. It was found that the L-DOPA agent (at conc. 10 g L-1) significantly improved the IFSS of the composites up to 27%. Also, the L-DOPA coating (at conc. 40 g L-1) significantly increased the glass fibre strength up to 18%. As a result, an optimum coating level could be tailored depending on application and whether fibre strength or IFSS was of greater importance. In addition, SEM and TGA analyses were used to detect and quantify the coating agents. FTIR and XPS further confirmed presence of the coating and indicated the zwitterionic crystals of L-DOPA and the formation of a melanin-like polymer layer. The spectroscopy data also evidenced that both catechol and amine groups contributed to the interaction between the L-DOPA and the PGF surface.

Through-and-through stab wound of the cervical spinal canal with retained weapon but no neurological repercussions: an exceptionally rare injury and the case for direct withdrawal. Illustrative case.

BACKGROUND: Nonmissile penetrating spinal injuries are rare and potentially debilitating. Such injuries can sometimes be complicated by the retention of a foreign body, which is usually part of the assailant's weapon, making their management even more problematic. OBSERVATIONS: We present a unique case of stab wound to the neck with a retained ice pick, traversing the spinal canal from one intervertebral foramen to the other, yet with no ensuing neurological damage to the patient. After carefully analyzing the weapon's trajectory on computed tomography and ruling out vertebral artery injury via catheter angiography, the ice pick was successfully withdrawn under general anesthesia and intraoperative neurophysiological monitoring, averting the need for a more invasive surgical procedure. LESSONS: Stab wounds of the spinal canal with a retained foreign body can occasionally be managed by direct withdrawal. Whether this simple technique is a safe alternative to open surgical exploration should be determined on a case-by-case basis after careful review of spinal and vascular imaging. The absence of significant neurological or vascular injury is an absolute prerequisite for attempting direct withdrawal. Moreover, preparations should be made for possible conversion to open surgical exploration in the rare event of active hemorrhage, expanding hematoma, or acute neurological deterioration.

Addressing Atropisomerism in the Development of Sotorasib, a Covalent Inhibitor of KRAS G12C: Structural, Analytical, and Synthetic Considerations.

Nearly a century after its first description, configurationally stable axial chirality remains a rare feature in marketed drugs. In the development of the KRASG12C inhibitor sotorasib (LUMAKRAS/LUMYKRAS), an axially chiral biaryl moiety proved a critical structural element in engaging a "cryptic" protein binding pocket and enhancing inhibitor potency. Restricted rotation about this axis of chirality gave rise to configurationally stable atropisomers that demonstrated a 10-fold difference in potency. The decision to develop sotorasib as a single-atropisomer drug gave rise to a range of analytical and synthetic challenges, whose resolution we review here.Assessing the configurational stability of differentially substituted biaryl units in early inhibitor candidates represented the first challenge to be overcome, as differing atropisomer stability profiles called for differing development strategies (e.g., as rapidly equilibrating rotamers vs as single atropisomers). We relied on a range of NMR, HPLC, and computational methods to assess atropisomer stability. Here, we describe the various variable-temperature NMR, time-course NMR, and chiral HPLC approaches used to assess the configurational stability of axially chiral bonds displaying a range of rotational barriers.As optimal engagement of the "cryptic" pocket of KRASG12C was ultimately achieved with a configurationally stable atropisomeric linkage, the second challenge to be overcome entailed preparing the preferred (M)-atropisomer of sotorasib on industrial scale. This synthetic challenge centered on the large-scale synthesis of an atropisomerically pure building block comprising the central azaquinazolinone and pyridine rings of sotorasib. We examined a range of strategies to prepare this compound as a single atropisomer: asymmetric catalysis, chiral chromatographic purification, and classical resolution. Although chiral liquid and simulated moving bed chromatography provided expedient access to initial multikilo supplies of this key intermediate, a classical resolution process was ultimately developed that proved significantly more efficient on metric-ton scale. To avoid discarding half of the material from this resolution, this process was subsequently refined to enable thermal recycling of the undesired atropisomer, providing an even more efficient commercial process that proved both robust and green.While the preparation of sotorasib as a single atropisomer significantly increased both the analytical and synthetic complexity of its development, the axially chiral biaryl linkage that gave rise to the atropisomerism of sotorasib proved a key design element in optimizing sotorasib's binding to KRASG12C. It is hoped that this review will help in outlining the range of analytical techniques and synthetic strategies that can be brought to bear in addressing the challenges posed by such axially chiral compounds and that this account may provide helpful guidelines for future efforts aimed at the development of such single atropisomer, axially chiral pharmaceutical agents.

Synthesis of Substituted Pyridines via Formal (3+3) Cycloaddition of Enamines with Unsaturated Aldehydes and Ketones.

An organocatalyzed, formal (3+3) cycloaddition reaction is described for the practical synthesis of substituted pyridines. Starting from readily available enamines and enal/ynal/enone substrates, the protocol affords tri- or tetrasubstituted pyridine scaffolds bearing various functional groups. This method was demonstrated on a 50 g scale, enabling the synthesis of 2-isopropyl-4-methylpyridin-3-amine, a raw material used for the manufacture of sotorasib. Mechanistic analysis using two-dimensional nuclear magnetic resonance (NMR) spectrometry revealed the transformation proceeds through the reversible formation of a stable reaction off-cycle species that precedes pyridine formation. In situ reaction progress kinetic analysis and control NMR studies were employed to better understand the role of FeCl3 and pyrrolidine hydrochloride in promoting the reaction.

Nutritional deficiency in an intestine-on-a-chip recapitulates injury hallmarks associated with environmental enteric dysfunction.

Environmental enteric dysfunction (EED)-a chronic inflammatory condition of the intestine-is characterized by villus blunting, compromised intestinal barrier function and reduced nutrient absorption. Here we show that essential genotypic and phenotypic features of EED-associated intestinal injury can be reconstituted in a human intestine-on-a-chip lined by organoid-derived intestinal epithelial cells from patients with EED and cultured in nutrient-deficient medium lacking niacinamide and tryptophan. Exposure of the organ chip to such nutritional deficiencies resulted in congruent changes in six of the top ten upregulated genes that were comparable to changes seen in samples from patients with EED. Chips lined with healthy epithelium or with EED epithelium exposed to nutritional deficiencies resulted in severe villus blunting and barrier dysfunction, and in the impairment of fatty acid uptake and amino acid transport; and the chips with EED epithelium exhibited heightened secretion of inflammatory cytokines. The organ-chip model of EED-associated intestinal injury may facilitate the analysis of the molecular, genetic and nutritional bases of the disease and the testing of candidate therapeutics for it.

REACT: Rapid Evaluation Assessment of Clinical Reasoning Tool.

INTRODUCTION: Clinical reasoning encompasses the process of data collection, synthesis, and interpretation to generate a working diagnosis and make management decisions. Situated cognition theory suggests that knowledge is relative to contextual factors, and clinical reasoning in urgent situations is framed by pressure of consequential, time-sensitive decision-making for diagnosis and management. These unique aspects of urgent clinical care may limit the effectiveness of traditional tools to assess, teach, and remediate clinical reasoning. METHODS: Using two validated frameworks, a multidisciplinary group of clinicians trained to remediate clinical reasoning and with experience in urgent clinical care encounters designed the novel Rapid Evaluation Assessment of Clinical Reasoning Tool (REACT). REACT is a behaviorally anchored assessment tool scoring five domains used to provide formative feedback to learners evaluating patients during urgent clinical situations. A pilot study was performed to assess fourth-year medical students during simulated urgent clinical scenarios. Learners were scored using REACT by a separate, multidisciplinary group of clinician educators with no additional training in the clinical reasoning process. REACT scores were analyzed for internal consistency across raters and observations. RESULTS: Overall internal consistency for the 41 patient simulations as measured by Cronbach's alpha was 0.86. A weighted kappa statistic was used to assess the overall score inter-rater reliability. Moderate reliability was observed at 0.56. DISCUSSION: To our knowledge, REACT is the first tool designed specifically for formative assessment of a learner's clinical reasoning performance during simulated urgent clinical situations. With evidence of reliability and content validity, this tool guides feedback to learners during high-risk urgent clinical scenarios, with the goal of reducing diagnostic and management errors to limit patient harm.